CLDN18.2 is a highly attractive therapeutic target in gastric cancer and other solid tumors and has become a major focus for therapeutic antibody development, including monoclonal antibodies, bispecific antibodies, ADCs, and CAR-T programs. However, antibody discovery against CLDN18.2 presents a unique challenge because CLDN18.2 and CLDN18.1 share extremely high sequence similarity and differ by only a few amino acids within their extracellular loops. Achieving high specificity therefore requires an antigen that preserves the native conformation of the protein in its natural membrane environment.
CLDN18.2 and 18.1 are alternative splicing variants from the same gene. There are only 9 amino acid different within ECL1.
Our CLDN18.2 Nanodisc is prepared using polymers that extract full-length CLDN18.2 along with its surrounding native membrane, maintaining the transmembrane structure and the correct presentation of extracellular loop epitopes. Using this Nanodisc antigen, we successfully generated antibodies that specifically recognize the ECL1 loop of human CLDN18.2 without cross-reacting with CLDN18.1, demonstrating the advantage of native membrane–supported antigens for developing highly selective binders.
Native membrane antigen for antibody discovery
• Full-length CLDN18.2 in its native membrane environment
• Maintains correct extracellular loop conformation
Discovery of conformation-dependent binders
• Stabilizes physiologically relevant extracellular epitopes
• Identifies CLDN18.2 antibodies with therapeutic potential
Detergent-free membrane protein analysis
• Soluble nanodisc format compatible with ELISA, SPR, and BLI
• Enables reliable affinity and kinetic measurements
SDS-PAGE
Functional ELISA
SPR
Used as an Immunogen to Produce antibodies
DIMA BIOTECHprovides full product solutions for CLDN18.2 specific therapeutic mAb development, including CLDN18.2 and CLDN18.1 recombinant proteins from different species, CLDN18.2 BMKs and CLDN18.2 Flow Cytometry-validated mAb and off-the-shelf lead mAbs for therapeutic mAb development. For off-the-shelf lead mAb program, please click here to see more.